1. Field of the Invention
The present invention relates generally to the field of molecular biology, cell biology, and medicine. More particularly, it concerns mixing or combining cultures of neurons derived from pluripotent stem cells and methods of using such mixed cell cultures.
2. Description of Related Art
The mammalian brain works appropriately only when there is a proper balance between excitation and inhibition. An imbalance in the excitatory-inhibitory (E/I) ratio is associated with abnormal sensory processing and unconsciousness (Zhang and Sun, 2011; Massimini et al., 2012). Increased E/I ratios can lead to prolonged neocortical circuit activity, stimulus hypersensitivity, cognitive impairments and epilepsy (Hagerman and Hagerman, 2002; Gibson et al., 2008: reviewed in Zhang and Sun, 2011). Similarly, decreases in the E/I ratio have been linked to abnormalities such as impaired social interaction and autistic behaviors, and mental retardation (Rett Syndrome) (Tabuchi et al., 2007; Dani et al., 2005; reviewed in Zhang and Sun, 2011). It has been well studied and determined that the E/I ratio changes during development, with excitation decreasing and inhibition increasing, and that deviations in these changes for either can disrupt the E/I ratio (reviewed in Zhang and Sun, 2011). With the dramatic rise in the incidence of neurological diseases, there is a need for improved therapies. However, access to clinically-relevant cell models continues to be a major challenge in neuroscience research and drug development. Human induced pluripotent stem cell (iPSC)-derived neurons provide a cell type that may be used to facilitate an improved understanding of the mechanisms of neurological diseases. Clearly, there is a need for in vitro approaches that can more effectively simulate in vivo systems.